These proposed studies directly address 3 RFA objectives. First, we offer a basic/translational science study that considers local urogenital tract factors in the pathogenesis of UCPPS. Second, we address RFA request for studies to identify and validate biomarkers for UCPPS. Our strategy uses cutting-edge proteomic analysis of urine specimens from patients with IC/PBS and CP/CPPS in a new approach to identify and validate new biomarkers that potentially could improve diagnosis, predict UCPPS natural history, and predict or measure response to treatment. Third, this work also addresses the RFA priority to elucidate the pathogenesis of UCPPS. These protein/peptide markers may act via specific cellular pathways important to UCPPS pathology. Notably, if successful, this technology can be exported across the Network and could establish a foundation for future clinical trials and for more targeted therapies to treat specific urothelial defects.